We have studied benzo(a)pyrene (BP) metabolism in human lymphocytes and monocytes; lymphocyte aryl hydrocarbon hydroxylase (AHH) activity and inducibility in normal humans, twins, lung cancer patients and their progeny; BP metabolism in human lymphocytes in long term culture; and the inducibility of the metabolic activation of BP in inbred strains of mice. We have studied and optimized various culture conditions- such as length of incubation, length of exposure to mitogens, type of mitogens, storage factors, medium ingredients etc.- for human lymphocyte AHH assay under conditions that yield reproducible results on the same individual over a period of time. Using these culture conditions, human population studies indicate that lymphocyte AHH inducibility is determined by a few genes; it is heritable in human population (heritability coefficient, 0.7); development of lung cancer, which may be related to metabolism of polycyclic aromatic hydrocarbons (PAHS), is unrelated to the heritability of lymphocyte AHH-inducibility. We also found that several PAHS and other compounds induce lymphocyte AHH activity; whereas alpha-napthoflavone decreases total metabolism of BP by human lymphocytes and monocytes, trichloropropene oxide prevents accumulation of BP-diols. We have also developed a sensitive assay to study metabolite profiles of BP produced by as little as 10 x 10 to the 6th power cells and resolved by HPLC. We have also identified, developed and optimized culture conditions for the metabolism of BP by a stable human lymphocyte cell line in permanent culture. Comparison between hepatic microsome-mediated AHH activity and DNA-alkylation by BP metabolites in various inbred strains of mice shows very strong association between the two activities.